FIG 3.

Metabolic modeling shows coordination of CcpA and CodY fluxes. (A) The solution of space of the models with CDM- and CDMG-specific metabolic constraints was sampled. The sum of sampled fluxes through CodY and CcpA reaction shows increased flux through CodY in CDMG. (B) Sampled fluxes through several amino acid biosynthetic pathways also show increased flux in CDMG. Definition of the biosynthetic pathways is found in Materials and Methods. (C) Flux through GLUDy reaction changes direction when glucose is added; alpha-ketoglutarate (AKG) is converted to l-glutamate in CDMG and vice versa in CDM. l-Glutamate is then utilized in biosynthesis of other amino acids in CDMG regenerating AKG. (D) Amino acids generated by accepting amine groups from l-glutamate, coupling the CcpA reaction GLUDy with amino acid-generating CodY reactions. (E) Metabolic map of folate cycle where CcpA and CodY regulated metabolism intersect. (F) Simulated flux through reactions in folate cycle in CDM and CDMG shows alternate metabolic reactions used in each medium. In CDM, reactions that consume glycine (GCC and GHMT2r) to interconvert between THF and methyl-THF (mlTHF). In CDMG, glycine is instead generated by GHMT2R running in reverse.